MCP-1 is known to be a monocyte chemotactic factor relating to inflammatory diseases, and belongs to CC chemokine sub-family. MCP-1 is found to express not only from monocyte but also from cardiac muscle cell, blood vessel endothelial cell, fibroblast, chondrocyte, smooth muscle cell, mesangial cell, aveolar cell, T lymphocyte, macrophage, etc. in various pathosis (specifically, angiostenosis, arteriosclerosis, rheumatic arthritis, diabetic microangiopathy, granulomatous inflammation (tuberculosis, sarcoidosis, etc.), solid cancer, diastolic cardiomyopathy (chronic heart failure, etc.), glomerulonephritis, etc.), and MCP-1 deeply relate to crisis and progression these pathosis. Therefore, MCP-1 receptor antagonists are used as a medicament for the treatment and prophylaxis of these pathosis.
So far, there have been only a little reports on low molecule compounds having antagonistic activity on MCP-1 receptor. For example, it is disclosed that aryloxy-propanolamine derivatives being active as .beta.-blocker show weak inhibitory activity on MCP-1 binding to its receptor in JP-A-25756/1995 and that phenylethanolamine derivatives having sympathetic activity and sympatholytic activity show weak inhibitory activity on MCP-1 binding to its receptor in JP-A-25757/1995.
On the other hand, phosphonic acid derivatives having osteogenesis activity is disclosed in JP-A-73476/1996 but there is no description on MCP-1 receptor antagonistic activity.
The present invention is to provide a new anilide derivative or a salt thereof having antagonistic activity on MCP-1 receptor and therapeutic and prophylactic effect on cardiac infarction, myocarditis, cardiomyopathy, chronic heart failure, restenosis after angioplasty, disorder after reperfusion in lung and heart, inflammatory diseases (e.g. arteriosclerosis, arteriosclerosis after heart transplantation, (chronic) rheumatic arthritis, nephritis, etc.), rejection after organ transplantation, fibroid lung, renal insufficiency, diabetic diseases (e.g. diabetes, diabetic nephropathy, diabetic complication, diabetic retinopathy, diabetic retinitis, diabetic microangiopathy, etc.), tumor (e.g. bladder cancer, breast carcinoma, cervical carcinoma, chronic lymphocytic leukemia, chronic myelocytic leukemia, colon carcinoma, multiple myeloma, malignant myeloma, prostatic cancer, lung cancer, stomach cancer, Hodgkin's disease, etc.) infectious diseases (e.g. tuberculosis, invasive staphylococcia, etc.), etc.; production method and use thereof.